Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression

Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response

Highly neurotic never-depressed students have negative biases in information processing

BACKGROUND: Cognitive theories associate depression with negative biases in information processing. Although negatively biased cognitions are well documented in depressed patients and to some extent in recovered patients, it remains unclear whether these abnormalities are present before the first depressive episode. METHOD: High neuroticism (N) is a well-recognized risk factor for depression. The current study therefore compared different aspects of emotional processing in 33 high-N never-depressed and 32 low-N matched volunteers. Awakening salivary cortisol, which is often elevated in severely depressed patients, was measured to explore the neurobiological substrate of neuroticism. RESULTS: High-N volunteers showed increased processing of negative and/or decreased processing of positive information in emotional categorization and memory, facial expression recognition and emotion-potentiated startle (EPS), in the absence of global memory or executive deficits. By contrast, there was no evidence for effects of neuroticism on attentional bias (as measured with the dot-probe task), over-general autobiographical memory, or awakening cortisol levels. CONCLUSIONS: These results suggest that certain negative processing biases precede depression rather than arising as a result of depressive experience per se and as such could in part mediate the vulnerability of high-N subjects to depression. Longitudinal studies are required to confirm that such cognitive vulnerabilities predict subsequent depression in individual subjects

Faces and Facets:Variability of Emotion Recognition in Psychopathy Reflect its Affective and Antisocial Features

Psychopathy consists of a constellation of affective-interpersonal features including lack of empathy, callousness, manipulativeness and interpersonal charm, impulsiveness and irresponsibility. Despite its theoretical and predictive value in forensic contexts, the relationships between the psychometric dimensions of psychopathy, including its antisocial features, and the construct’s neuropsychological characteristics remain uncertain. In this study, 685 personality-disordered prisoners with histories of serious violent or sexual offenses were assessed for psychopathy before completing a computerized and well-validated assessment of the ability to recognize emotional expressions in the face. Prisoners with more of the affective features of psychopathy, and prisoners with more of its antisocial manifestations, showed relatively poor recognition accuracy of fearfulness and disgust. These relationships were independent and modest but were still evident following correction for demographic features (e.g., ethnicity and socioeconomic status), mental illness (e.g., substance and alcohol misuse), personality disorders (other than antisocial personality disorder) and treatment status. By contrast, the associations between these dimensions of psychopathy and emotion recognition were diminished by controlling for cognitive ability. These findings demonstrate that variability in the ability of high-risk personality-disordered prisoners to recognize emotional expressions in the face—in particular, fear and disgust—reflects both the affective and antisocial aspects of psychopathy, and is moderated by cognitive ability. (PsycINFO Database Record (c) 2017 APA, all rights reserved

Effects of emotion recognition training on mood among individuals with high levels of depressive symptoms: study protocol for a randomised controlled trial.

BACKGROUND: We have developed a new paradigm that targets the recognition of facial expression of emotions. Here we report the protocol of a randomised controlled trial of the effects of emotion recognition training on mood in a sample of individuals with depressive symptoms over a 6-week follow-up period. METHODS/DESIGN: We will recruit 190 adults from the general population who report high levels of depressive symptoms (defined as a score ≥ 14 on the Beck Depression Inventory-II). Participants will attend a screening session and will be randomised to intervention or control procedures, repeated five times over consecutive days (Monday to Friday). A follow-up session will take place at end-of -treatment, 2-weeks and 6-weeks after training. Our primary study outcome will be depressive symptoms, Beck Depression Inventory- II (rated over the past two weeks). Our secondary outcomes are: depressive symptoms, Hamilton Rating Scale for Depression; anxiety symptoms, Beck Anxiety Inventory (rated over the past month); positive affect, Positive and Negative Affect Schedule (rated as 'how you feel right now'); negative affect, Positive and Negative Affect Schedule (rated as 'how you feel right now'); emotion sensitivity, Emotion Recognition Task (test phase); approach motivation and persistence, the Fishing Game; and depressive interpretation bias, Scrambled Sentences Test. DISCUSSION: This study is of a novel cognitive bias modification technique that targets biases in emotional processing characteristic of depression, and can be delivered automatically via computer, Internet or Smartphone. It therefore has potential to be a valuable cost-effective adjunctive treatment for depression which may be used together with more traditional psychotherapy, cognitive-behavioural therapy and pharmacotherapy. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN17767674.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Using an Experimental Medicine Model to Explore Combination Effects of Pharmacological and Cognitive Interventions for Depression and Anxiety

Selective serotonergic reuptake inhibitors (SSRIs) and cognitive therapies are effective in the treatment of anxiety and depression. Previous research suggests that both forms of treatments may work by altering cognitive biases in the processing of affective information. The current study assessed the effects of combining an SSRI with a cognitive intervention on measures of affective processing bias and resilience to external challenge. A total of 62 healthy participants were randomly assigned to receive either 7 days of citalopram (20 mg) or placebo capsules while also completing either an active or a control version of a computerized cognitive bias training task. After treatment, standard measures of affective processing bias were collected. Participants' resilience to external stress was also tested by measuring the increase in negative symptoms induced by a negative mood induction. Participants who received both citalopram and the active cognitive bias training task showed a smaller alteration in emotional memory and categorization bias than did those who received either active intervention singly. The degree to which memory for negative information was altered by citalopram predicted participants' resistance to the negative mood induction. These results suggest that co-administration of an SSRI and a cognitive training intervention can reduce the effectiveness of either treatment alone in terms of anxiety- and depression-relevant emotional processing. More generally, the findings suggest that pinpointing the cognitive actions of treatments may inform future development of combination strategies in mental health

Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers

Anxiety is associated with threat-related biases in information processing such as heightened attentional vigilance to potential threat. Such biases are an important focus of psychological treatments for anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of a range of anxiety disorders. The aim of this study was to assess the effect of an SSRI on the processing of threat in healthy volunteers. A selective noradrenergic reuptake inhibitor (SNRI), which is not generally used in the treatment of anxiety, was used as a contrast to assess the specificity of SSRI effects on threat processing. Forty-two healthy volunteers were randomly assigned to 7 d double-blind intervention with the SSRI citalopram (20 mg/d), the SNRI reboxetine (8 mg/d), or placebo. On the final day, attentional and interpretative bias to threat was assessed using the attentional probe and the homograph primed lexical decision tasks. Citalopram reduced attentional vigilance towards fearful faces but did not affect the interpretation of ambiguous homographs as threatening. Reboxetine had no significant effect on either of these measures. Citalopram reduces attentional orienting to threatening stimuli, which is potentially relevant to its clinical use in the treatment of anxiety disorders. This finding supports a growing literature suggesting that an important mechanism through which pharmacological agents may exert their effects on mood is by reversing the cognitive biases that characterize the disorders that they treat. Future studies are needed to clarify the neural mechanisms through which these effects on threat processing are mediated

Short-term escitalopram treatment normalizes aberrant self-referential processing in major depressive disorder

Background: Increased self-focus and negative self-concept play an important role in depression. Antidepressants influence self-referential processing in healthy volunteers, but their function in self-processing of depressed patients remains unknown. Methods: Thirty-two depressed patients were randomly allocated to receive either escitalopram 10 mg or placebo for one week. After one week, neural responses to positive and negative self-referential adjectives and neutral control stimuli were assessed with functional magnetic resonance imaging. A group of matched healthy volunteers served as a control group. Results: Escitalopram decreased responses of medial fronto-parietal regions to self-referential words relative to non-emotional control stimuli, driven by increased responses to the control condition. Escitalopram also increased responses in the pre-defined region of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) to positive relative to negative words. Importantly, the changes in neural responses occurred before any effect on depressive symptoms, implying a direct effect of escitalopram. Furthermore, the placebo group had decreased responses of the MPFC and the ACC to positive self-referential processing relative to the matched healthy controls. However, neural responses of the escitalopram group and the healthy unmedicated controls were similar. Limitations: Differences between the groups in self-reported depression symptoms and personality traits may have influenced the results. Conclusion: One-week treatment with escitalopram normalized aberrant self-referential processing in depressed patients, shifting the focus from the self to the external environment and potentiating positive self-referential processing. This may be an important factor in mechanism of action of antidepressants.Peer reviewe

Brain activity measured by functional brain imaging predicts breathlessness improvement during pulmonary rehabilitation

Background Chronic breathlessness in chronic obstructive pulmonary disease (COPD) is effectively treated with pulmonary rehabilitation. However, baseline patient characteristics predicting improvements in breathlessness are unknown. This knowledge may provide better understanding of the mechanisms engaged in treating breathlessness and help to individualise therapy. Increasing evidence supports the role of expectation (ie, placebo and nocebo effects) in breathlessness perception. In this study, we tested functional brain imaging markers of breathlessness expectation as predictors of therapeutic response to pulmonary rehabilitation, and asked whether D-cycloserine, a brain-active drug known to influence expectation mechanisms, modulated any predictive model. Methods Data from 71 participants with mild-to-moderate COPD recruited to a randomised double-blind controlled experimental medicine study of D-cycloserine given during pulmonary rehabilitation were analysed (ID: NCT01985750). Baseline variables, including brain-activity, self-report questionnaires responses, clinical measures of respiratory function and drug allocation were used to train machine-learning models to predict the outcome, a minimally clinically relevant change in the Dyspnoea-12 score. Results Only models that included brain imaging markers of breathlessness-expectation successfully predicted improvements in Dyspnoea-12 score (sensitivity 0.88, specificity 0.77). D-cycloserine was independently associated with breathlessness improvement. Models that included only questionnaires and clinical measures did not predict outcome (sensitivity 0.68, specificity 0.2). Conclusions Brain activity to breathlessness related cues is a strong predictor of clinical improvement in breathlessness over pulmonary rehabilitation. This implies that expectation is key in breathlessness perception. Manipulation of the brain’s expectation pathways (either pharmacological or non-pharmacological) therefore merits further testing in the treatment of chronic breathlessness

Within-Network Connectivity in the Salience Network After Attention Bias Modification Training in Residual Depression: Report From a Preregistered Clinical Trial

Alterations in resting state networks (RSNs) are associated with emotional- and attentional control difficulties in depressed individuals. Attentional bias modification (ABM) training may lead to more adaptive emotional processing in depression, but little is known about the neural underpinnings associated with ABM. In the current study a sample of 134 previously depressed individuals were randomized into 14 days of computerized ABM- or a closely matched placebo training regime followed by a resting state magnetic resonance imaging (MRI) scan. Using independent component analysis (ICA) we examined within-network connectivity in three major RSN’s, the default mode network (DMN), the salience network (SN) and the central executive network (CEN) after 2 weeks of ABM training. We found a significant difference between the training groups within the SN, but no difference within the DMN or CEN. Moreover, a significant symptom improvement was observed in the ABM group after training.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02931487

Does repeatedly viewing overweight versus underweight images change perception of and satisfaction with own body size?

Body dissatisfaction is associated with subsequent eating disorders and weight gain. One-off exposure to bodies of different sizes changes perception of others' bodies, and perception of and satisfaction with own body size. The effect of repeated exposure to bodies of different sizes has not been assessed. We randomized women into three groups, and they spent 5 min twice a day for a week completing a one-back task using images of women modified to appear either under, over, or neither over- nor underweight. We tested the effects on their perception of their own and others' body size, and satisfaction with own size. Measures at follow-up were compared between groups, adjusted for baseline measurements. In 93 women aged 18–30 years, images of other women were perceived as larger following exposure to underweight women (and vice versa) (p < 0.001). There was no evidence for a difference in our primary outcome measure (visual analogue scale own size) or in satisfaction with own size. Avatar-constructed ideal (p = 0.03) and avatar-constructed perceived own body size (p = 0.007) both decreased following exposure to underweight women, possibly due to adaptation affecting how the avatar was perceived. Repeated exposure to different sized bodies changes perception of the size of others' bodies, but we did not find evidence that it changes perceived own size